DSpace Collection:http://localhost:8081/xmlui/handle/123456789/24
Sun, 07 Jun 2020 09:37:34 GMT2020-06-07T09:37:34ZSYNTHESIS OF HETEROCYCLIC COMPOUNDS OF BIOLOGICAL INTERESThttp://localhost:8081/xmlui/handle/123456789/14754
Title: SYNTHESIS OF HETEROCYCLIC COMPOUNDS OF BIOLOGICAL INTEREST
Authors: Kumar, Sandeep
Abstract: For human beings inflammatory diseases and cancer continue to be serious health problems. A number of anti-inflammatory drugs and a few anticancer drugs are available in the market. At present anti-inflammatory drugs available have serious side effects such as gastric ulcer, kidney damage & heart failure etc. Need for safer anti-inflammatory drugs and more anticancer drugs exist. There is an urgent need to identify new potent anti-inflammatory and anticancer molecules which can be developed as anti-inflammatory and anticancer drugs. Efforts have been made by us in this direction, which is described in this thesis. For the sake of clarity, the work embodied in thesis is divided into five chapters. First Chapter : General introduction: In part Ia of this this chapter recent work on the use of microwave technology in organic synthesis reported in literature is summarized. In part Ib recent work reported in literature on the synthesis, anti-inflammatory and anticancer activities of acridine, bisacridine, pyrazole, oxadiazole, isoindole, pyrrolopyrazine, amidine, azomethine, benzimidazole and piperazine derivatives is summarized. All the new compounds synthesized and reported in the following chapters were charaterized by IR, 1H NMR, 13C NMR, Mass (GC-MS, APCI-MS) spectroscopy and elemantal analysis.
Second Chapter: In this chapter synthesis of bisacridine derivatives IIIa-j and Va-j by following reaction Scheme 2.1 & 2.2 is discussed. NNCSRR1H2NR2NH2IVa-eIIa,bVa-j For Compounds Va-jScheme:-2.2 Synthesis of bisacridine derivatives Va-jNHNRR1CSHNR2NHCSHNNRR1 R R1 R2Vf H H Vg CH3 H Vh OCH3 H Vi H CH3 Vj H OCH3NN(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3 R R1 R2Va H H Vb CH3 H Vc OCH3 H Vd H CH3 Ve H OCH3NN(CH2)3(CH2)3NN(CH2)3(CH2)3NN(CH2)3(CH2)3NN(CH2)3(CH2)3THFstirring atRT, 6hNClRR1NHNRR1R2NHNR1RH2NR2NH2RefluxMeOHIa-eIIa,bIIIa-j For Compounds IIIa-j R R1 R2IIIf H H IIIg CH3 H IIIh OCH3 H IIIi H CH3 IIIj H OCH3NN(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3OOOO(CH2)3(CH2)3Scheme:-2.1 Synthesis of bisacridine derivatives IIIa-j R R1 R2IIIa H H IIIb CH3 H IIIc OCH3 H IIId H CH3 IIIe H OCH3NN(CH2)3(CH2)3NN(CH2)3(CH2)3NN(CH2)3(CH2)3NN(CH2)3(CH2)317-18 h
ii
Compounds IIIa-j and Va-j were screened for anti-inflammatory activity at 50mg/kg p.o. Compound IIIg exhibited 41% anti-inflammatory activity whereas standard drug ibuprofen exhibited 39% activity at 50 mg/kg p.o. Anticancer activity evaluation against five human cancer cell lines i.e. lung (NCI H-522), ovary (PA-1), breast (T47D), colon (HCT-15) and liver (HepG2) at a concentration of 1× 10-5M, indicate that compound IIIh possess good anticancer activity i.e. 76%, 81%, 86% and 67% against first four cancer cell lines whereas compound IIIa exhibited good anticancer activity i.e. 50% against liver (HepG-2) cancer cell line.
Third Chapter: In this chapter synthesis of pyrazole derivatives i.e. IIa-j (Scheme 3.1) and oxadiazole derivatives i.e. IVa-f (Scheme 3.2) using microwave irradiation technique is described.
Pyrazole and oxadiazole derivatives (IIa-l, IVa-f) were screened for anti-inflammatory activity at 50mg/kg p.o. and for anticancer activity against five human cancer cell lines (mentioned in chapter-2) at a concentration of 1× 10-5M. Compound IIj and IVh exhibited 35% anti-inflammatory activity as compared to ibuprofen which showed 39% activity at 50 mg/kg p.o. Compound IVd exhibited 48% and 39% anticancer activity against lung (NCI H-522) & liver (HepG2) and compound IIj show 41% anticancer activity against breast (T47D) cancer cell lines. Fourth Chapter: It is divided into two parts i.e. 4a and 4b. Part 4a: deals with the synthesis of azomethine (VIax-cz) and amidine (VIIax-cz) derivatives of isoindole (IIIa, b) and pyrrolopyrazine (IIIc) by following reaction Scheme 4a.1.
ZYXCOCHCHRZYXNNR1RR1NHNH2H2OMWI, 3 min X Y Z R R1IIa N CH CH H IIb CH N CH HIIc CH CH N HIId N CH CH HIIe CH N CH HIIf CH CH N HIa-f IIa-lOCH3H3CONMe2OCH3H3COOCH3H3CONMe2NMe2Scheme-3.1: Synthesis of pyrazole derivatives X Y Z R R1IIg N CH CH PhIIh CH N CH PhIIi CH CH N Ph IIj N CH CH PhIIk CH N CH PhIIl CH CH N PhOCH3H3CONMe2OCH3H3COOCH3H3CONMe2NMe2YXZNH2NOHYXZNONRMWI, 7 min IIIa-c IVa-fOHOCH3OCH3H3COOCH3H3COOCH3H3COOHOCH3OHOCH3Scheme-3.2: Synthesis of oxadiazole derivatives X Y Z RIVd N CH CHIVe CH N CHIVf N CH N X Y Z RIVa N CH CHIVb CH N CHIVc N CH N X Y Z IIIa N CH CHIIIb CH N CHIIIc N CH NRCHO
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Azomethine derivatives i.e. (VIax-cz) and amidine derivatives (VIIax-cz) were screened for anti-inflammatory activity at 50mg/kg p.o. and for anticancer activity against five human cancer cell lines i.e. breast (T47D), lung (NCI H-522), colon (HCT-15), ovary (PA-1) and liver (HepG2) at a concentration of 1× 10-5M. Compound VIIcx exhibited good anti-inflammatory activity i.e. 35% as compared to standard drug ibuprofen which showed 39% activity at 50 mg/kg p.o.. Compounds VIbz, VIIcx, VIIcz (breast T47D), VIbz, VIcy (lung NCI H-522), VIbx, VIIbz (colon HCT-15), VIbz (ovary PA-1) and VIbx, VIcz (liver HepG-2) exhibited good anticancer activity.
Part 4b: deals with the synthesis of isoindole, pyrrolopyrazine, benzimidazoisoindole and benzimidazopyrrolopyrazine derivatives i.e. IIIx-z, IVx-z; VIxa-ze and VIIxa-ze by following reaction Scheme 4b.1.
COOHCOOHR1R1NOONH2+Grinding/RTIa-cIIIa-cH2NNH2H2OR1NOONR1NOONCHR2CNH2R3R2CHOR3CNVIax-czVIIax-czMWIIVx-zVx-zMWIIINNScheme 4a.1 Synthesis of azomethine & amidine derivatives of isoindole & pyrrolopyrazine IIIa-c, VIax-cz & VIIax-cz.For compound Ia-c & IIIa-cR1, a=; R1, c=; R1, b= R1 R2 VIax VIay VIaz VIbx VIby R1 R2 VIbz VIcx VIcy VIczOHOCH3OCH3H3CONCH3CH3OHOCH3OCH3H3CONNNNNNNCH3CH3OHOCH3OCH3H3CONCH3CH3 R1 R2 VIIax VIIay VIIaz VIIbx VIIby R1 R2 VIIbz VIIcx VIIcy VIIczNNNNNNNNNNNNNNNNNN30 min6 min6 minH2NH2NCOOHCOOHRRNOOCOOHH2NRNONCOOH+MWIMWIRNOOH2NRNONOHNR1HNOR1Ix-zIIIx-zIVx-zVIxa-zeR1NH2R1NH2Ix = R =NNIy = R =Iz = R =Va-eVa-eCOOHVIIxa-zeGrinding, RTGrinding, RTIIScheme 4b.1 Synthesis of compounds IIIx-z, IVx-z, VIxa-ze, VIIxa-ze. R R1 VIxa, VIIxa VIxb, VIIxb VIxc, VIIxc VIxd, VIIxd VIxe, VIIxe R R1 VIya, VIIya VIyb, VIIyb VIyc, VIIycVIyd, VIIydVIye, VIIyeH2CNH2CNH2CNH2CH2COH2CNH2CNH2CNH2CH2CO R R1 VIza, VIIza VIzb, VIIzb VIzc, VIIzcVIzd, VIIzdVIze, VIIzeH2CNH2CNH2CNH2CH2CONNNNNNNNNN5 min5 min20 min20 min
iv
Compounds VIyc and VIIzd exhibited good anti-inflammatory activity i.e. 34% and 37% as compared to standard drug ibuprofen which showed 39% activity at 50 mg/kg p.o. Compounds VIzc, VIIzd (lung NCI H-522), VIye, VIIxd, VIIyd, VIIzc, VIIzd (colon HCT-15), VIxc, VIIzc (ovary PA-1), VIxc, VIyb, VIzc (liver Hep G-2) exhibited good anticancer activity.
Fifth Chapter: contains microwave assisted synthesis of piperazine-2,6-dione (IIIa-l) and 4-(1H-indole-2 carbonyl)piperazine-2,6-dione (IVa-l) derivatives by following reaction scheme 5.1. It also contain synthesis of bis piperazine-2,6-dione derivatives (VIax-jz) by following reaction scheme 5.2.
HNCOOHCOOHH2NR1+HNNR1OONNR1OONHNHCOOHMWIMWI, 7 minCOIVa-lR1 is same for IIa-l, IIIa-l & IVa-lIIa-lIIIa-lINNCH2CH2CH2NH2CNH2CNH2CSH2COH2CH2CNCH2CH2CH2ONCH2CH2ONCH2CH2SCH2CH2Scheme 5.1 Synthesis of piperazine-2,6-dione (IIIa-l) and 4-(1H-indole-2-carbonyl)piperazine-2,6-dione (IVa-l) derivatives. R1 a b c d R1 e f g h R1 i j k l3 minHOOCR2COOHHNNR1OOCR2COONNR1OONNR1OO+MWIScheme 5.2 Synthesis of heterocyclic compounds VIax-VIjzNNSIIIa-jVx-zVx R2= ; Vy R2= ; Vz R2=VIax-jz R1IIIaIIIb IIIc IIId IIIeNH2CNH2CNH2CSH2COH2CH2CN(CH2)3ON(CH2)2IIIf IIIg IIIh IIIi IIIjNNSNN(CH2)3NH2CNH2C R1 R2VIaxVIay VIaz VIbxVIby VIbzVIcxVIcy VIcz VIdxNN(CH2)3NN(CH2)3NNSNH2CNH2CNNSNNH2CSH2COH2CNH2C R1 R2VIdy VIdz VIexVIey VIezVIfxVIfy VIfz VIgxVIgyNNSNNSNNSNNH2CNH2CNH2CSH2CSH2COH2CH2CN(CH2)2OH2C R1 R2VIgz VIhxVIhy VIhzVIixVIiy VIiz VIjxVIjyVIjzNNSNNSNNSNH2CH2CN(CH2)3ON(CH2)2N(CH2)2N(CH2)3ON(CH2)3O11-12 minNN(CH2)3
v
Compounds IIIa-l and IVa-l and VIax-jz were screened for anti-inflammatory activity at 50mg/kg p.o. and for anticancer activity against five human cancer cell lines i.e. breast (T47D), lung (NCI H-522), colon (HCT-15), ovary (PA-1) and liver (HepG2) at a concentration of 1× 10-5M. Biological evaluation reveals that compounds VIbx and VIex possess anti-inflammatory activity 43% and 39% respectively, which is comparable or better than ibuprofen (a standard drug) which exhibited 39% activity at 50 mg/kg p.o. Compounds VIax exhibited anticancer activity 28% against breast (T47D); VIay 39% against lung (NCI H-522); IIIj 49% against colon (HCT-15); IVe 42% against ovary (PA-1) and IIIh, IVf 46%, 45% respectively against liver (HepG2) cancer cell lines. All these compounds exhibited moderate to good anticancer activity against the cell lines mentioned above. Conclusion: In this thesis synthesis, characterization, anti-inflammatory and anticancer activity evaluation of more than one hundred forty compounds is reported. Compounds IIIg (Chapter 2), VIbx, VIex, VIcx, VIdx, IVe (Chapter 5) and VIIzd (Chapter 4b) exhibited anti-inflammatory activity comparable or better than standard drug ibuprofen. Compounds IIIh, IIIi (Chapter 2) against lung (NCI H-522); IIIf, IIIh, IIIi, IIIf (Chapter 2) against ovary (PA-1); IIIh (Chapter 2) against breast (T47D); IIIh (Chapter 2) against colon (HCT-15) and IIIa (Chapter 2), VIxc (Chapter 4b), IIIh, IVf (Chapter 5) against liver (HepG2) exhibited good anticancer activity against various cancer cell lines mentioned above. One compound IIIh (Chapter 2) exhibited good anticancer activity against all the cancer cell lines screened except one i.e. liver (HepG2) cancer cell line. Compounds which exhibited good anti-inflammatory and anticancer activities can be candidate for further studies. From the work reported in this thesis three research papers have been published and three are under review in various international journals.Mon, 01 Jul 2013 00:00:00 GMThttp://localhost:8081/xmlui/handle/123456789/147542013-07-01T00:00:00ZSYNTHESIS, CHARACTERIZATION AND CATALYTIC ASPECTS OF DIOXIDOMOLYBDENUM(VI) COMPLEXEShttp://localhost:8081/xmlui/handle/123456789/14740
Title: SYNTHESIS, CHARACTERIZATION AND CATALYTIC ASPECTS OF DIOXIDOMOLYBDENUM(VI) COMPLEXES
Authors: Dhaka, Sarita
Abstract: Chemical reactions generally proceed through the breaking and formation of
bonds between atoms in molecules to produce new compounds. In a general sense,
anything that increases the rate of any process is often called “catalyst”, a term derived
from Greek 􀈛ατα􀈜ϑǫ􀈚υ, meaning “to annul”, or “to untie”, or “to pick up”. The catalyst
decreases the activation energy of a reaction by altering the reaction path but it itself
remains unchanged. The word “catalysis” was probably used first time in the sixteenth
century by the chemist A. Libavious. These days catalysts are playing a vital role in
petrochemicals, fine chemicals, pharmaceuticals, fertilizers and food industries. The
biochemically significant processes are also based on catalysts.
Sometimes chemists surprise the nature, which is a foundation of motivation, by
mimicking its complex reactions like most popular mimetic approach of molybdenum
compounds. Initially Bortels highlighted the biological importance of molybdenum
compounds in 1930. Oxyanion molybdate is the soluble biological active form of
molybdenum. On one hand molybdenum is a minor constituent of the earth's crust and on
the other hand it is widely bioavailable due to the high solubility of molybdate salts in
water, the most abundant transition metal in seawater. Molybdenum is the single 4d
transition metal, present in biological a system which outlines the part of the lively site of
molybdoenzymes that accomplish the key transformations in the metabolism of nitrogen,
sulfur and carbon compounds. On the basis of amino acid sequences, spectroscopic
properties, active site structures and catalyzed reactions molybdenum containing enzymes
can be distributed in many classes. R. Hille gave a classification of molybdoenzymes
with the help of rapidly growing number of X-ray crystal structures, which is based on
structural homology of the active sites. Two different types of molybdoenzymes are
acknowledged: Molybdenum nitrogenase which catalyzes the reduction of atmospheric
dinitrogen to ammonia and another types of molybdoenzymes are oxidoreductases such
as aldehyde oxidase, xanthine oxidase, sulfite oxidase, nitrate reductase and xanthine
dehydrogenase that transfer an oxido group or two electrons to from the substrate. The
IV
enormous majority of these molybdoenzymes acquire at least one Mo=O unit in their
active sites and are frequently named as oxidomolybdenum enzymes.
Upon going through the literature, it is evident that molybdenum Schiff base
complexes have provided opportunities to develop catalytic system for various industrial
processes. Particularly, oxidation reactions catalyzed by these specialized complexes are
well documented. However, in most cases optimization of the reaction conditions to
effect maximum efficiency of the catalysts have not been set out. It was, therefore,
reasonable to undertake systematic study on the synthesis and characterization of new
molybdenum catalysts and to explore their catalytic potential for the oxidation of
organic substrates under optimized reaction conditions.
First chapter is the introductory one and describes a variety of molybdenum
complexes that have been used as homogeneous catalysts in different types of organic
transformations. Literature on the catalytic applications of various
dioxidomolybdenum(VI) complexes has also been reviewed.
In Second Chapter, the dioxidomolybdenum(VI) complexes [MoVIO2(Hsaldahp)(
H2O)] (2.1), [MoVIO2(Hclsal-dahp)(H2O)] (2.2) and [MoVIO2(Hbrsal-dahp)(H2O)]
(2.3) have been prepared by the reaction of [MoVIO2(acac)2] (Hacac = acetylacetone)
with tribasic pentadentate Schiff bases H3sal-dahp (2.I), H3clsal-dahp(2.II) and H3brsaldahp(
2.III) (sal = salicylaldehyde, clsal = 5-chlorosalicylaldehyde, brsal = 5-
bromosalicylaldehyde, dahp = 1,3-diamino-2-hydroxypropane) in methanol at reflux
condition. Reactions of these complexes with pyridine result in the formation of
[MoVIO2(Hsal-dahp)(py)] (2.4), [MoVIO2(Hclsal-dahp)(py)] (2.5) and [MoVIO2(Hbrsaldahp)(
py)] (2.6). These complexes have been used as catalysts for the oxidation of
methyl phenyl sulfide, benzoin and oxidative bromination of styrene efficiently using
H2O2 as green oxidant. Oxidation of methyl phenyl sulphide under the optimized reaction
conditions gave ca. 98 % conversion with two major products methyl phenyl sulfoxide
and methyl phenyl sulfone in the ca. 66.8 % and 33.2 % selectivity, respectively. The
oxidation of benzoin, catalyzed by MoVIO2 complexes was carried out in refluxing
methanol which gave 95% conversion in 4 h of reaction time and the selectivity of the
V
reaction products varied in the order: benzoic acid (40) > methyl benzoate (32 %), >
benzil (15%) > benzaldehyde-dimethylacetal (13 %). The oxidative bromination of
styrene using molybdenum complexes as catalyst precursors gave 98% conversion and
the selectivity of different major products followed the order: phenylethane-1,2-diol
(67%) > 1,2-dibromo-1-phenylethane (21%) > 2-bromo-1-phenylethane-1-ol (3%).
Third Chapter describes the synthesis of [MoVIO2{Hdfmp(sbdt)2}(H2O)] (3.1),
[MoVIO2{Hdfmp(smdt)2}(H2O)] (3.2) and [MoVIO2{Hdfmp(tsc)2}(H2O)] (3.3) by the
reaction of [MoVIO2(acac)2] with the tribasic pentadenate O, N and S donor ligands
H3dfmp(sbdt)2 (3.I), H3dfmp(smdt)2 (3.II) and H3dfmp(tsc)2 (3.III) derived from 2,6-
diformyl-4-methylphenol and S-benzyldithiocarbazate, S-methyldithiocarbazate, and
thiosemicarbazide. These complexes were characterized using spectroscopic studies (IR,
UV/Vis and NMR), elemental analyses, thermal studies and single crystal study which
reveal that only one set of azomethine nitrogen, enthiolate sulfur and phenolate oxygen
atoms of the ligands are coordinated to the molybdenum. Oxidations of styrene and
cyclohexene have been investigated using these complexes as catalyst precursors in the
presence of H2O2 as oxidant in the presence of NaHCO3. Under the optimized reaction
conditions, a maximum of 96 % conversion of styrene has been obtained with 3.1, 98 %
conversion with 3.2 and 97 % conversion with 3.3 in 2 h of reaction time. The selectivity
of the products is similar for the catalyst precursors (i.e. complexes 3.1 to 3.3) and
follows the order: styrene oxide > phenyl acetaldehyde. With cyclohexene, a maximum
conversion of 96% has been achieved with 3.1, 94 % with 3.2 and 96 % conversion with
3.3, also in 2.5 h of reaction time and cyclohexene oxide is formed as a product with 100
% selectivity. UV-Vis experiment with all complexes confirm the plausible formation of
MoVI O(O2)L as intermediates in the catalytic oxidations.
New dioxidomolybdenum(VI) complexes, [MoVIO2{Hdfmp(bhz)2}(MeOH)]
(4.1), [MoVIO2{Hdfmp(inh)2}(MeOH)] (4.2) and [MoVIO2{Hdfmp(nah)2}(MeOH)] (4.3)
of ligand H3dfmp(L)2 obtained by the condensation of 2,6-diformyl-4-methylphenol
(dfmp) and hydrazides (L) [L = benzoylhydrazide (bhz), isonicotinoylhydrazide (inh),
and nicotinoylhydrazide (nah)], respectively. Studies on these complexes are described in
VI
Fourth Chapter. All complexes are characterized by various physico-chemical studies.
Oxidation of secondary alcohols: 1-phenyl ethanol, 2-propanol and 2-butanol, catalyzed
by these molybdenum complexes, using conventional liquid phase and microwaveassisted
methods in the presence of 30 % H2O2 as an oxidant have been tested. The
effects of various factors, such as temperature and amounts of catalyst, H2O2 and solvent
have been investigated. These alcohols under the optimized reaction conditions gave high
yields of the respective ketone. Addition of an N-based additive reduces the reaction time
considerably. Amongst the two methods studied, the microwave technique proves to be a
time efficient system.
In Fifth Chapter the synthesis of dioxidomolybdenum(VI) complexes,
[MoVIO2(fhmc-bhz)(MeOH)] (5.1), [MoVIO2(fhmc-inh)(MeOH)] (5.2) [MoVIO2(fhmcnah)(
MeOH)] (5.3) and [MoVIO2(fhmc-fah)(MeOH)] (5.4) have been described. These
complexes are obtained by the reaction of [MoVIO2(acac)2] and potential ONO tridentate
ligands H2fhmc-bhz (5.I), H2fhmc-inh (5.II), H2fhmc-nah (5.III), and H2fhmc-fah (5.IV),
derived from condensation of equimolar amount of 8-formyl-7-hydroxy-4-
methylcoumarin (fhmc) and hydrazides [benzoylhydrazide (bhz), isonicotinoylhydrazide
(inh), nicotinoylhydrazide (nah) and furoic acid hydrazide (fah)] in methanol. The
structures of the obtained ligands and their respective metal complexes were elucidated
by elemental analyses, spectroscopic techniques (IR, electronic, 1H and 13C NMR) and
thermogravmetric analyses. These metal complexes have been tested against oxidative
bromination of monoterpene (thymol) by using H2O2 as an oxidant. Therefore, they act as
functional models of vanadium dependent haloperoxidases. A maximum of 94%
conversion has been achieved where selectivity of different major products follows the
order: 2,4-dibromothymol (84.6%) > 2-bromothymol (8.4%) > 4-bromothymol (7%). The
effects of various factors, such as amounts of catalyst, oxidant, KBr, HClO4 and different
solvents have been considered to optimize the reaction conditions for the maximum
brominated products.
Finally, summary and over all conclusions based on the achievements are
presented.Fri, 01 May 2015 00:00:00 GMThttp://localhost:8081/xmlui/handle/123456789/147402015-05-01T00:00:00ZDESIGN AND SYNTHESIS OF FLUORESCENCE TURN-ON CHEMOSENSORS FOR SOME METAL IONShttp://localhost:8081/xmlui/handle/123456789/14725
Title: DESIGN AND SYNTHESIS OF FLUORESCENCE TURN-ON CHEMOSENSORS FOR SOME METAL IONS
Authors: Naveen, Mergu
Abstract: Over the past few years, high sensitive and selective fluorescent chemosensors towards
various transition and other toxic metal ions are particularly attractive to current researchers
due to its potential applications in the medicinal, clinical and environmental research areas. At
present, many techniques are available for qualitative and quantitative analysis of metal ions
and found their applications in various food, biological, geological and industrial effluents
such as atomic absorption spectroscopy, inductively coupled plasma-mass spectroscopy,
inductively coupled plasma emission spectrometry, neutron activation analysis,
chromatography and voltammetry. Nevertheless, most of these methods involve tedious
sample preparation procedures, sophisticated instruments and high maintenance expenditure.
In recent years there has been a growing need for constructing chemical sensors for fast, ontime
and cost-effective monitoring of environmental samples. The research and development
(R&D) in the sensors area has expanded exponentially in terms of financial investment,
numbers of paper published, and the number of active researchers worldwide. Compared with
the traditional analysis instruments, chemical sensors are portable, simple to use, in-situ and
miniature in size. These features are ideal for real-time on field measurements, thus the errors
caused by the sample transportation and storage can be largely reduced. On the other hand,
fluorescent chemosensors have drawn attention and offer considerable advantages over other
techniques via their simplicity, convenience, low-cost, sensitivity, immediate response, and
naked-eye visualization.
The thesis is divided into six chapters. General introduction and a survey of
fluorescence-based optical sensors reported in the literature are presented in Chapter 1. These
chemosensors are typically derived from a core group of well-known fluorophores, such as
coumarin, bipyridine, indole, quinoline, calixarene, porphyrin, crown ether, fluorescein,
rhodamine, BODIPY and nanoparticle, each emitting in different regions of the
electromagnetic spectrum.
Chapter 2 describes the theory which involves during the sensing process. Details
related to the photoluminescence process will be discussed in the different subsections. The
properties of excited states as well as their relaxation processes are explained with the help of
Jablonski diagram. Classification of chemosensors according to the nature of the signal
ii
emitted by the active unit and the different possible mechanisms such as PET, ICT and ET for
signal transduction upon analyte binding to chemosensors, and the terms used in the study of
fluorescence sensing have also been discussed in this chapter.
In Chapter 3, the fluorescent sensors C1 and C2 with 4-aminoantipyrine unit have
been prepared and characterized. Their complexation behaviour and binding mode towards
Al3+ and other metal ions have been studied by UV–Vis, fluorescence spectrometric and
HRMS methods. The free ligands C1 and C2 exhibited a main absorption band at about 345
nm and 380 nm, respectively. On the addition of metal ions to sensors, a new broad absorption
band (mainly for Cu2+, Ni2+, Co2+ and Al3+ ions) was observed at 350–480 nm region.
Receptor C1 and C2 alone displayed a very weak single fluorescence emission band at 498
nm and 484 nm respectively, with an excitation of 360 nm. On addition of Al3+, receptors C1
and C2 exhibited a prominent fluorescence enhancement accompanied by a blue shift of 32
nm from 498 to 466 nm and 18 nm from 484 to 466 nm, respectively. Indicating that the
receptors C1 and C2 exhibit “off-on” mode with high sensitivity towards Al3+ over other
metal ions which are used. The 1H NMR titrations were carried out to explore the nature of
interaction between receptor and aluminum ion. These sensors are successfully applied in
highly acidic and neutral pH medium with the fastest response time (<5 sec). The fluorescence
color change could be easily detected by the naked eye under a UV lamp. Fluorescence
quenching of complex is observed in the presence of Cu2+, Ni2+ and Co2+ ions due to
dissociation of Al3+ complex of receptor.
N
N
O
N Ar
C1: Ar = 2-hydroxyphenyl
C2: Ar = 2-hydroxynaphthyl
Chart 1. Structures of the antipyrine based sensors.
In Chapter 4, new fluorescence chemosensors, CS1 and CS2 based on flavonol
derivatives were synthesized and characterized. Complexation behaviour of sensors towards
zinc and other tested metals have been studied using UV–Vis and fluorescence spectrometric
methods. The free ligands CS1 and CS2 exhibited a main absorption band centred at 343 nm
iii
and 356 nm, respectively. On the addition of metal ions to sensors, the absorption band of free
receptors CS1 and CS2 is shifted to low intensity, while a new broad absorption band (mainly
for Cu2+, Ni2+, Zn2+, Pb2+, Al3+, Co2+, Cd2+, Mn2+ and Mg2+ ions) was observed at about 350–
480 nm region. Chemosensors CS1 and CS2 alone displayed a weak single fluorescence
emission band at 530 nm and a couple of emission bands at 425 and 530 nm, respectively,
with an excitation of 340 nm. On addition of Zn2+, receptors CS1 and CS2 exhibited a
prominent fluorescence enhancement accompanied by a blue shift of 54 nm from 530 to 476
nm and 52 nm from 530 to 478 nm, respectively. These reveal selective detection towards
Zn2+ ion, along with fluorometric response. Also, those serve as a highly selective
chemodosimeter for Zn2+ at neutral pH with naked-eye detection and successfully examined
the reversibility of Chemosensor–Zn(II) complexation.
O
O
OH
Ar
CS1: Ar = Phenyl
CS2: Ar = 2-furyl
Chart 2. Structures of the flavonol based sensors.
In Chapter 5, a simple 4-Methyl-7-hydroxy-8-formyl Coumarin serves as a selective
chemosensor for Mg2+ in the presence of alkali and alkaline earth metal ions. The free ligand
CS exhibited a single absorption band at about 343 nm, hyperchromic shift was observed
when added to Co2+, Cu2+, Gd3+, Mg2+, Mn2+, Nd3+, Ni2+ and Zn2+ ions. It showed a blue shift
accompanied by a hyperchromic shift in the presence of Cr3+ and Al3+ metal ions.
Chemosensor alone showed a single emission band at 473 nm with an excitation of 350 nm.
CS showed a chelation enhanced fluorescence (CHEF) only with Mg2+, even though there was
a relatively chelation enhanced fluorescent quenching (CHEQ) effect with Al3+, Co2+, Cr3+,
HO O O
CHO
4-Methyl-7-hydroxy-8-formyl Coumarin
Chart 3. Structure of the Coumarin based sensor.
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Cu2+, Fe2+, Gd3+, Mn2+, Nd3+, Ni2+ and Zn2+. It showed a significant fluorescence enhancement
and provides naked-eye detection towards Mg2+. The receptor exhibited a good binding
constant and lowest detection limit for Mg2+. The variation of emission signal exists via of
reversible chelation enhanced fluorescence (CHEF) with this inherent quenching metal ion.
In Chapter 6, a series of rhodamine derivatives have been prepared and characterized
by FT-IR, 1H NMR, 13C NMR and ESI-MS, and their colorimetric and fluorescence responses
toward various metal ions were explored. Ligand L1–L4 shows fluorescence response to Al3+
in the presence of other competing metal ions in methanol. The detection limit of Al(III) was
estimated based on the fluorescence titration profile as 6.0×10−7 M (for L1), 5.8×10−7 M (for
L2), 5.0×10−7 M (for L3) and 1.4 × 10−7 M (for L4). The resultant Al3+ complex of the sensor
L4 is evaluated for anion recognition properties. The metal complex is highly selective for the
determination of AcO− and F− with a detection limit of 0.4 μM in same solvent. The sensors,
RS1 and RS2 exhibited highly selective and sensitive “turn-ON” fluorescent and colorimetric
response toward Cr3+. The detection limit of Cr(III) was calculated for RS1 and RS2 as
4.9×10−8 M and 2.4×10−7 M, respectively. Receptor RH exhibited strong colorimetric
response toward Cu(II), Al(III) and Fe(III) and specific fluorometric response to Fe(III) in
semi aqueous medium. The formation of RH–Al3+ complex is fully reversible and can sense to
AcO− and F− via dissociation. Thus, the sensor RH provides fluorescence “off-on-off” strategy
for the sequential detection of Al3+ and AcO−/F−. All these rhodamine-derived sensors works
on the basis of structure change from spirocyclic form (fluorescence “OFF”) to ring-opened
amide form (fluorescence “ON”) induced by a specific chemical species such as ionic metal at
room temperature. Upon the addition of metal ion, the spiro ring was opened and the complex
was formed in a 1 : 1 stoichiometry, and it was further confirmed by ESI-MS spectra.
N O N
N
O
N
Ar
RS1: Ar = 2-hydroxynaphthyl
RS2: Ar = 2,4-dihydroxyphenyl
O
N
N
N O
N
O
O
N
N
O N
N
O
R
L1: R = Ethylene
L2: R = 1,3-propylene
L3: R = Oxydiethylene
N O N
N
O
N
L4: Ar = 4-hydroxy-3-methoxyphenyl
RH: Ar = 2,5-dihydroxyphenyl
Ar
Chart 4. Structures of the rhodamine based chemosensorsThu, 01 Oct 2015 00:00:00 GMThttp://localhost:8081/xmlui/handle/123456789/147252015-10-01T00:00:00ZELECTROANALYTICAL STUDIES ON SOME ION SELECTIVE MEMBRANES ELECTRODEShttp://localhost:8081/xmlui/handle/123456789/14687
Title: ELECTROANALYTICAL STUDIES ON SOME ION SELECTIVE MEMBRANES ELECTRODES
Authors: Bharti, Arvind Kumar
Abstract: Detection of environmental pollutants both organic and inorganic has been a major challenge to analytical chemists. In recent years many instrumental techniques viz., Electro- thermal atomization-Atomic absorption spectroscopy (ETA-AAS), Inductively coupled plasma-Atomic emission spectrometry (ICP-AES), Neutron activation analysis, Ion chromatography, High performance liquid chromatography [HPLC], Flame photometry and Cyclic voltametry have been used for the quantitative analysis of pollutants. All these listed techniques are sophisticated, time consuming and costly and require huge infrastructure and expert handling. On the other hand Ion-selective electrodes (ISEs) provide an analytical procedure that is simple, convinces and fast. Analysis by Ion-selective electrode can be carried out in field and is also adaptable to online monitoring another major advantage of analysis by ISEs i.e. requires minimum chemical manipulation of sample and is applicable to turbid as well coloured solution.
Ion-selective electrodes are extensively used for determining concentration of various ions in bloods, biological fluids, eatables, drugs etc. One of the important applications of ion- selective electrodes is the monitoring of toxic metals in effluents and natural waters. Some of the established applications of ISEs are determination of F– in drinking water, Ca2+ in dairy products, determination of promethium in spiked water sample and K+ in fruit juices etc. They are also used to determine clinically important ions viz., Na+, K+, Li+ and Ca2+
A survey of literature reveals that a number of Ion-selective electrodes have been developed for various metals and anions. However the availability of Ion-selective electrode for metal such as molybdenum, promethium, fluoride and mercury is rather limited. These are some reported electrode for these metals but they exhibits certain limitation such as short in body fluids. They have also been used to determine metals in soils, fertilizers and plant products.
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working range, poor selectivity and higher response times. Thus improved Ion-selective electrode for these metals are requested attempts in this direction we initiated by us. To develop good ion-selective electrodes ionophores having high affinity for a particular ionic species is required. Different types of material such as solid electrolytes in other multivalent metals, ion exchange, macrocyclic, calixarene and Schiff base have been used for this purpose. We have used some Schiff base, calixarene and macrocycle to develop ion-selective membrane electrodes for molybdenum, promethium, fluoride and mercury. The result of this investigation is incorporated in the present thesis divided into six chapters which are discussed briefly here.
First chapter presents a “General Introduction” which describes the background of the research work, the problem statement and objectives of the present study. The chapter also summarized a review of good ion-selective electrodes for alkali metal ion, alkaline earth metal ion, rare earth metal ion, transition metal and anions.
Second Chapter presents; “Theory and Methodology of Ion Selective Membranes Electrodes” This chapter describes the classification of ion-selective electrodes, theory of membrane potentials and parameters of ion-selective electrodes, the terms selectivity used in the study of ion selective electrode. The selectivity of an ion selective membrane is a measure of the selectivity of an electrode for the primary ion in the presence of interfering species. The degree of selectivity of the electrode is given by Eisenman-Nicolsky equation
For determination of Selectivity coefficient three methods are used.
1. Separate Solution method
2. Mixed solution method
+±=Σ≠BABBzAzBPotBAAAaKaFzRTEE/,0)(log303.2
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3. Fixed Interference Method
Third Chapter; this chapter reveal a “Promethium ion-selective sensor based on the comparative study of two Schiff base ligands as neutral ionophores” have been developed and effect of various plasticizers have been studied. Two Schiff base ligands (3,5:12.14:21,23-tribenzo-8,9:17,18:26,27-tricyclohexyl-1,6,10,15,19,24-hexaazo-[27]-1,6,10,15,19,24-triene (X1) and 15,17,32,34-tetramethyl-3,29-dioxa-11,12,16,20,21,35-hexaazapentacyclo[29.3.1. 114,18.04,9.023,28]hexatriaconta 1(35),4,6,8,10,14(36),15,17,21,23,25,27,31,33-tetradecaene-13,19-dione (X2)) as neutral ionophores and effect of various plasticizers: 2-nitrophenyl- octylether (o-NPOE), dibutyl phosphonate (DBP), dioctylphthalate (DOP), tri-(2-ethylhexyl) phosphate (TEHP), dibutyl butylphosphonate (DBBP), 1-chloronaphthalene (1-CN) and anion excluders: potassium tetrakis(p-chloropheny1) borate (KTpClPB), sodium tetraphenylborate (NaTPB) and oleic acid (OA) have been studied. The membrane with a composition of ionophore (X1/X2):KTpClPB:PVC:o-NPOE (w/w, %) in the ratio of 5:5:30:60 exhibited best performance. The best responsive membrane sensors (8 and 21) exhibited working concentration range of 4.5 × 10−7 – 1.0 × 10−2 mol L-1 and 3.5 × 10−6 – 1.0 × 10−2 mol L-1 with a detection limits of 3.2 × 10−7 mol L-1 and 2.3×10−6 mol L-1 and Nernstian slopes of 20.0 ± 0.5, 19.5 ± 0.5mV decade−1
The fourth Chapter; “A comparative study on PVC based sensors in determination of the Molybdenum”, deals with Ion-selective electrode based on macrocyclic for selective determination of molybdenum. Three macrocyclic 4,8-diaza-3,3,10,10-tetramethyl-1,2- of activity, respectively. The sensor no. 8 works satisfactorily in partially non-aqueous media up to 10% (v/v) content of methanol, ethanol and acetonitrile. Analytical application of the proposed sensor has been demonstrated in determination of promethium(III) ions in spiked water samples and the electrode could be used successful in water sample.
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dithiacyclodecane(S1), 5,8-diaza-3,3,10,10-tetramethyl-1,2-dithiacyclodecane-N,N”-diacetic
acid (S2) and N,N”-bis(2,2-dimethyl-2-mercaptoethyl)ethylenediamine-N,N-diacetic acid (S3)
when prepared and preliminary studies shows that macrocyclic neutral ionophores shows high
affinity of molybdenum. These three membranes are used to develope molybdenum selective
membrane electrode. A number of membrane prepared of three macrocyclic separately,
number of PVC base three membrane prepared and investigated, the result have shown the
sensor using as three ionophore perform best. The performance of electrodes adding the
different plasticizer, It was found that ortho nitro phenyl octylether (o-NPOE) is the best
plasticizer and potassium tetrakis(p-chlorophenyl) borate (KTpClPB) best cationic additives.
The membrane having composition (w/w, mg%); 5.0(S):30.0(PVC):5.0 (KTpClPB):60.0(o-
NPOE), performed best in respect of different performance characteristic. It exhibits a wide
working concentration range 2.3 × 10–7 – 1.0 × 10–2 mol L–1 with a detection limit of 1.2 × 10–7
mol L–1 and slope of 11.2 decades-1
The fifth chapter; “A comparative study of fluoride selective PVC based
electrochemical sensors”: this chapter reports PVC based membrane electrodes based on four
ionophore M
of activity. The sensor was found to be sufficient effective
for the Molybdenum and it can be used to determine the concentration in different sample.
The electrodes have a shelf life time of 2-5 months and dynamic response time of 11s.
1–M4 (Ionophore M1, meso-octamethylcalix[4]pyrrole. Ionophores M2,
[7H,23H-34,39-etheno-6,43;24,30 dimethenotribenzo [o,v,g] [1,4,7,11,34] trioxadiazacyclo
heptatriacontine-7,23-dione,8,9,10,11,13,14,16,17,19,20,21,22,31,32,33,40,41,42-octadeca
hydro-44,45,46,47-tetrahydroxy-32,41-bis(methylene). Ionophore M3, is 7H,23H-34,39-
etheno-6,43;24,30-dimethenotribenzo[o,v,g] [1,4,7,11,34] trioxadiazacycloheptatriacontine-
7,23-boropyrene,8,9,10,11,13,14,16,17,19,20,21,22,31,32,33,40,41,42-octadecahydro- 44, 45,
46,47-tetrahydroxy-32,41-bis(methylene) and ionophore M4; dinitrophenyl functionalized trisv
(amide)) which have been synthesized and characterized by IR, 1H NMR, spectroscopic
investigations indicate good affinity of these ligands for fluoride anion. Different polyvinyl
chloride (PVC) based membranes of ligands have been synthesized using different cationic
excluders; CTAB, TDMAC, HTAB, ToMACI and plasticizers; DBBP, DBP, o-NPOE, CN,
DOP, TEHB and investigated as F− -selective sensors. The best performance is observed by
the sensor with a membrane of composition (%, w/w) M1:PVC:o-NPOE:CTAB
3.5:30.0:63.0:3.5. The sensor generates linear potential response over a wide working
concentration range of 2.5 × 10−7 to 1.0 × 10−2 mol L-1 with Nernstian slope (59.8 mV
decade−1 of activity) over a pH range of 2.5–6.5 with a fast response time of ∼11 s. It shows
good selectivity for fluoride anion (F−
The final and Sixth chapter “Mercury selective potentiometric sensor based on low
rim functionalized thiacalix[4]-arene as a cationic receptor”: this is the last chapter it report
the result of potentiometric sensor of mercury prepared by calixarene. PVC membrane of
these calixarene where prepared and studied as a mercury selective electrodes. It was found
that this membrane shows potential responses to mercury, the effect of plasticizer and
performances of membrane electrodes also studies. This describes a novel potentiometric
mercury(II) sensor based on the use of cation receptor 5,11,17,23-tetra-tert-butyl-25,27-
dihydroxy-26,28-bis(O-methylglycylcarbonylmethoxy)thiacalix[4]-arene in poly(vinyl chlorid
-e) (PVC) matrix for detection of Hg
) in preference to many anions. The sensor exhibits a
shelf life of two and half months and could be successfully used for the comparative
determination of fluoride contents in various samples. The proposed method is faster, cheaper
and more accurate in comparison to already used methods.
2+ has been developed. The sensor exhibits best
performance with a membrane composition of PVC:o-NPOE:Ionophore:NaTPB of
60:120:5:10 (%, w/w). The sensor selectively used for determination of mercury ions is in the
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concentration range 5.0 × 10−8 – 1.0 × 10−2 mol L-1 with a lower detection range of the order
1.0 × 10−8 mol L-1 and a Nernstian compliance of (29.5) within pH range 6.0 to 7.5 and fast
response time of 10 s. it can also be worked satisfactory. Selectivity coefficient of the
electrode shows the high affinity to Hg+2 over a number of metal ions. Influence of the
membrane composition and possible interference of other ions have also been investigated on
the response properties of the sensor, fast and stable response, good reproducibility and longterm
stability of the sensor are demonstrated. It has been observed that the developed sensor
satisfactorily works in partially non-aqueous media up to 10% (v/v) content of methanol and
acetonitrile and could be used for a period of 2.5 months. Selectivity coefficients determined
with fixed interference method (FIM) and match potential method (MPM) indicate high
selectivity towards mercury(II) ions. The proposed electrode shows fairly good discrimination
of mercury from other cations. The developed mercury ion-selective electrode can be
successfully employed as an indicator electrode in potentiometric titration with EDTA.Sat, 01 Feb 2014 00:00:00 GMThttp://localhost:8081/xmlui/handle/123456789/146872014-02-01T00:00:00Z